ArticlePsychoneuroendocrinology2009
Puberty, steroids and GABA(A) receptor plasticity.
Article in Psychoneuroendocrinology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 2 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
33 citing papers in PubMed, 2 syntheses or guidelines pooled it, 45 citations in OpenAlex.
- Comparison of central precocious puberty frequency before and during COVID-19: a systematic review and meta-analysis.BMC endocrine disorders · 2024Pooled it
- Cys-loop receptors on cannabinoids: All high?Frontiers in physiology · 2022Pooled it
- Progesterone improves cognitive performance and attenuates smoking urges in abstinent smokers.Psychoneuroendocrinology · 2011Trial
- Sleep deprivation impairs information processing via dysregulation of chloride homeostasis in the prefrontal cortex.bioRxiv : the preprint server for biology · 2026Article
- GABA system as the cause and effect in early development.Neuroscience and biobehavioral reviews · 2024Review
- Structural insights into opposing actions of neurosteroids on GABANature communications · 2023Article
- Endocrinological Involvement in Children and Adolescents Affected by COVID-19: A Narrative Review.Journal of clinical medicine · 2023Review
- Article
- GABA System Modifications During Periods of Hormonal Flux Across the Female Lifespan.Frontiers in behavioral neuroscience · 2022Review
- Early and precocious puberty during the COVID-19 pandemic.Frontiers in endocrinology · 2022Review
- Activity-based anorexia animal model: a review of the main neurobiological findings.Journal of eating disorders · 2021Review
- α4βδ-GABAJournal of neuroscience research · 2018Article
- Comparison of αβδ and αβγ GABAPharmacological research · 2018Review
- α4-GABAMolecular and cellular neurosciences · 2018Article
- Sex-dependent effects of nicotine on the developing brain.Journal of neuroscience research · 2017Review
- Review
- Mad men, women and steroid cocktails: a review of the impact of sex and other factors on anabolic androgenic steroids effects on affective behaviors.Psychopharmacology · 2016Review
- Flumazenil decreases surface expression of α4β2δ GABAA receptors by increasing the rate of receptor internalization.Brain research bulletin · 2016Article
- Article
- Animal models of absence epilepsies: what do they model and do sex and sex hormones matter?Neurobiology of disease · 2014Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
GABA(A) receptors (GABAR) mediate most inhibition in the CNS and are also a target for neuroactive steroids such as 3alpha,5[alpha]beta-THP (3alphaOH-5[alpha]beta-OH-pregnan-20-one or [allo]pregnanolone). Although these steroids robustly enhance current gated by alpha1beta2delta GABAR, we have shown that 3alpha,5[alpha]beta-THP effects at recombinant alpha4beta2delta GABAR depend on the direction of Cl(-) flux, where the steroid increases outward flux, but decreases inward flux through the receptor. This polarity-dependent inhibition of alpha4beta2delta GABAR resulted from an increase in the rate and extent of rapid desensitization of the receptor, recorded from recombinant receptors expressed in HEK-293 cells with whole cell voltage clamp techniques. This inhibitory effect of 3alpha,5[alpha]beta-THP was not observed at other receptor subtypes, suggesting it was selective for alpha4beta2delta GABAR. Furthermore, it was prevented by a selective mutation of basic residue arginine 353 in the intracellular loop of the receptor, suggesting that this might be a putative chloride modulatory site. Expression of alpha4betadelta GABAR increases markedly at extrasynaptic sites at the onset of puberty in female mice. At this time, 3alpha,5[alpha]beta-THP decreased the inhibitory tonic current, recorded with perforated patch techniques to maintain the physiological Cl(-) gradient. By decreasing this shunting inhibition, 3alpha,5[alpha]beta-THP increased the excitability of CA1 hippocampal pyramidal cells at puberty. These effects of the steroid were opposite to those observed before puberty when 3alpha,5[alpha]beta-THP reduced neuronal excitability as a pre-synaptic effect. Behaviorally, the excitatory effect of 3alpha,5[alpha]beta-THP was reflected as an increase in anxiety at the onset of puberty in female mice. Taken together, these findings suggest that the emergence of alpha4beta2delta GABAR at the onset of puberty reverses the effect of a stress steroid. These findings may be relevant for the mood swings and increased response to stressful events reported in adolescence.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.